Examining the potentials of stem cell therapy in reducing the burden of selected non-communicable diseases in Africa

Stem cell therapy (SCT) is a promising solution for addressing health challenges in Africa, particularly non-communicable diseases (NCDs). With their regenerative potential, stem cells have the inherent capacity to differentiate into numerous cell types for tissue repair. Despite infrastructural, ethical, and legal challenges, SCT holds immense promise for managing chronic illnesses and deep-seated tissue injuries. The rising prevalence of NCDs in Africa highlights the need for innovative strategies and treatment options. SCT offers hope in combating conditions like burns, osteoarthritis, diabetes, Alzheimer’s disease, stroke, heart failure and cancer, potentially reducing the burden of NCDs on the continent. Despite SCT’s opportunities in Africa, there are significant obstacles. However, published research on SCT in Africa is scarce, but recent initiatives such as the Basic School on Neural Stem Cells (NSC) express interest in developing NSC research in Africa. SCT research in African regions, notably on neurogenesis, demonstrates a concentration on studying neurological processes in indigenous settings. While progress has been made in South Africa and Nigeria, issues such as brain drain and impediments to innovation remain. Clinical trials have investigated the efficacy of stem cell treatments, emphasising both potential benefits and limitations in implementing these therapies efficiently. Financing research, developing regulatory frameworks, and resolving affordability concerns are critical steps toward realizing the potential of stem cell treatment in Africa.


Introduction
Stem cells, basic undifferentiated cells, hold great potential in regenerative medicine.There are promises for Africa's tissue regeneration and engineering, which could be revolutionised by stem cell therapy (SCT) [1,2].SCT stimulates, regulates, and modulates the body's endogenous stem cells while rejuvenating tissues and maintaining their original characteristics [1].They are an essential component of medical research and therapy and are categorised based on their origin as embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), or mesenchymal stem cells (MSCs) [2].By harnessing the clinical potential of stem cells and their derivatives, SCT stimulates the body's innate healing capabilities to repair damaged and malfunctioning tissues [3].They replace damaged cells and tissues, perhaps eliminating the need for costly, lifelong treatment modalities [3,4].Africa's health issues could be resolved by leveraging stem cells' diagnostic and therapeutic capabilities to cure various chronic illnesses, wounds, and impairments [3,5].Stem cells can differentiate into cell types to repair damaged tissues, such as neurons, cardiac, and liver cells, based on the body's needs [4,5].They are classified as totipotent, multipotent, unipotent, or pluripotent based on their differentiating capacity [2,3,5].Additionally, they have anti-inflammatory qualities, promote epithelial cell growth, and stop wounds from scarring, while the neurological system and bone tissue regeneration are significantly aided [5].However, despite its enormous potential advantages, infrastructural, ethical, and legal considerations must be addressed to guarantee its safe and efficient clinical application [4].
The burden of non-communicable diseases (NCDs) is becoming a global and public health concern, especially in Africa.Conditions such as burns, osteoarthritis, cancer, cardiovascular diseases (CVDs), diabetes, Alzheimer's disease, spinal cord injuries, heart failure and stroke are increasing, posing a substantial threat in the region (Fig. 1) [13].These diseases are becoming more prevalent than communicable diseases as the leading cause of death among those under the age of 70, fuelled by recent socioeconomic, demographic, and epidemiological dynamics in the region (Fig. 2) [13,14].The World Health Organisation (WHO) estimates that NCDs cause an annual loss of nearly 2.4 trillion dollars to Africa's gross domestic product.[6,7].Consequently, to address this trend, research on SCT potentials is recommended [14,15].Significant advancements have been made in developing technologies to tackle diseases in Africa, even though most gene therapy research is being carried out outside the continent.This limits the long-term feasibility of addressing NCDs in Africa, including the ability to treat inherited diseases, eradicate cancer, and inactivate viruses.A comprehensive analysis is crucial to assess the effectiveness of SCT and identify opportunities to enhance region-specific medical interventions [15].Thus, this study aims to explore the current state, challenges, Fig. 1 Comparison of prevalence and disability-adjusted life years for stem cell treatable diseases.[6][7][8][9][10][11][12] and potential clinical applications of stem cell therapy for NCDs in Africa.

Historical development and advancement of stem cell therapy
Exploring the field of stem cell biology, Ernst Haeckel, a well-known German biologist, used the phrase "stem cell" in 1868 to delineate the prodigious capacity of fertilized eggs to produce all cells in an organism [17].This discovery marked the beginning of the field of stem cell biology.In 1888, Theodor Heinrich Boveri and Valentin Haecker, who were German zoologists, described stem cells as a distinct cell population within embryos capable of developing into specialised cells, marking the first inception of stem cell treatment [18].In 1902, histologist Franz Ernst Christian Neumann and chemist Alexander Alexandrowitsch Maximov discovered common progenitor cells and developed the concept of polyblasts, which were later known as stem cells by Haeckel [19,20].Maximov's research highlighted the bone marrow's hematopoietic potential [20].A crucial preliminary advancement in using stem cell treatment in medicine was the 1939 case report detailing the human bone marrow transplant to cure an aplastic anaemia patient [21].
In 1958, French oncologist George Mathe performed the first stem cell transplant, a significant milestone in the history of the process.This procedure involved using bone marrow transplantation for the treatment of six nuclear researchers who had suffered from harmful radiation exposure at work [22].Furthering the scientific understanding of SCT, Mathe's groundbreaking work was continued in 1963 when he successfully performed a bone marrow transplant on a patient diagnosed with leukaemia [23].Meanwhile, the pioneering method of allogeneic hematopoietic stem cell transplantation (HSCT) was undertaken by Dr. E. Donnall Thomas, who performed the first successful allogeneic transplant in 1957.Nevertheless, the early attempts were not without difficulties.The ambiguities and risks surrounding bone marrow transplantation led to high mortality rates and poor engraftment success in the earliest investigations [24].Despite these obstacles, considerable advancements were made; for example, the success of allogeneic transplantation for diseases like acute myeloid leukaemia and aplastic anaemia was made possible by the discovery of cyclosporine in 1972 [25].The first umbilical cord blood stem cell transplant was subsequently carried out in 1988 on a kid suffering from Fanconi's anaemia, signalling the start of a new era in stem cell transplantation.A major Fig. 2 Morbidity and mortality rate of stem cell treatable diseases [6][7][8][9][10][11][12]16] step towards the general availability of SCT was the formation of the first public and private stem cell banks in the United States in 1992 [26,27].Later research revealed that these cells differed from the hematopoietic population and proliferated quickly in tissue culture vessels as adherent cells.The research team observed the ability of these cells to differentiate into osteoblasts, adipocytes, and chondrocytes in suspension culture, following their capability to generate colony-forming units (CFUs) from bone marrow.The term "mesenchymal stem cells" subsequently replaced earlier terms like "osteogenic" or "stromal stem cells" after the discovery of human embryonic stem cells (hESCs) in 1991 [28].
The past decades have witnessed notable advances in SCT research and development.Evans, Kaufman, Smithies, and Capecchi were awarded the 2007 Nobel Prize in Physiology or Medicine for their pioneering work in stem cell biology, which included the successful production of mouse embryonic stem cells in a lab setting in 1981 [27].The discovery of human induced pluripotent stem cells (iPS) in 2007 and human embryonic stem cells by James Alexander Thomson in 1998 expanded the scope of stem cell therapies and research.The field's progress has led to significant advancements, such as the therapeutic potential of umbilical cord stem cells, which are now seen as equally valuable as bone marrow stem cells [29].The first report on adult stem cell transplantation from umbilical cords was published in 2001, sparking further research into their clinical applications.In 2004, Gesine Koegler and associates discovered pluripotent stem cells in umbilical cord blood, adding to the growing body of evidence supporting the therapeutic potential of stem cells [30].Shinya Yamanaka and John Gurdon's 2012 Nobel Prize in Physiology or Medicine recognised their groundbreaking discovery that mature cells could be reprogrammed into stem cells, opening new possibilities for stem cell manipulation and pluripotency [31].
Advancements in stem cells and regenerative medicine have revolutionised the biomedical sector since the 20th century, fostering the management of NCDs, and extending human life expectancy and overall quality of life (Tables 1 and 2) [32].Blastocyst-derived adult stem cells (ASCs) and embryonic stem cells (ESCs) have emerged with exceptional therapeutic features.In animal investigations, ESCs have fostered brain regeneration, indicating they can self-regenerate and differentiate into all tissue types in vivo [4].Derived from the blastocysts' inner cell mass (ICM), pluripotent human embryonic stem cells (hESCs) can differentiate into any cell type in the body.Thereafter, they become multipotent stem cells that differentiate into numerous cell types found in particular germ layers [3].In contrast, adult stem cells with the capacity for multidirectional differentiation include MSCs obtained from the early mesoderm [33].These are microscopically extracted from bone marrow, dental pulp, adipose tissue, umbilical cord, and other tissues.The advantages of MSCs include their low immunogenicity, high expansion potential, and ease of isolation.In addition to hESCs and MSCs, other stem cell types, such as urine-derived stem cells, neural stem cells (NSCs), dental stem cells (DSCs), and myogenic stem cells (MDSCs), offer promising pathways for tissue regeneration [34].

The current state of stem cell research in Africa
Research has been limited on NSCs in the African SCT research community.However, the inaugural Basic School on NSC, funded by the International Brain Research Organisation African Regional Committee IBRO-ARC, brought together early-career neuroscientists and clinicians from South Africa, Uganda, and Nigeria [15,43], launching a new era in which scientists have explored the potential of SCTs for managing neurodegenerative illnesses and CNS regeneration.This has resulted in a growing body of research and a noticeable concentration of investigations in recent years.Currently, research is focused on neurogenesis using animal models, and laboratories in South Africa and Nigeria have actively investigated neurogenesis in rare African animals.Additionally, new research has begun to investigate the role of NSCs in human diseases, particularly rare familial syndromes, using translational and basic experimental methods [43,44].hESCs in innovative medication discovery and screening are changing the narrative in Africa, while ASCs are being experimented with bone marrow transplants for disorders such as myeloma [44,45].
South Africa leads other countries in stem cell research, attracting patients from all over the continent seeking therapy for blood and cancer-related illnesses.Institutions like Netcare Femina Hospital in Pretoria, the University of Pretoria, and the University of Cape Town actively participate in stem cell research, demonstrating the country's leadership in the field [45].Egypt had a haematopoietic stem cell transplantation programme in 1989, a significant milestone in the region's stem cell therapy landscape.This programme has evolved, with over 1320 transplants completed in the first 18 years of its operation [46,47].In Nigeria, the first successful stem cell transplant was performed in 2011 on a sickle cell anaemia patient at the University of Benin Teaching Hospital [48].Since then, six more successful transplants have been reported.The Bone Marrow Registry, Nigeria (BMRN) was established in 2012 to improve global recovery statistics for Africans with blood disorders.BMRN plans to launch Africa's first umbilical cord blood bank to support HSCT [49].Stem cell research has also Current research and collaborations promise additional advances in stem cell therapy in Africa in the coming years.SCT in Africa reveals a substantial gap compared to other continents, with only a few clinical trials in the region.Currently, just 2.5% of the global mesenchymal stem cell clinical trials are conducted in Africa, starkly contrasting the statistics across North America, Asia and Europe [50].Pluripotent stem cell clinical studies are also limited in Africa, with very few trials reported on the continent [50].However, there is a rising interest in investigating the potential of stem cells in treating heart disorders [51].Despite this, stem cells are mostly used as experimental models in vitro rather than for therapy, highlighting a need for additional research and development efforts to bridge the gap and fully realise the potential of stem cell treatment in Africa [51].

Challenges to stem cell therapy in Africa
Numerous factors have challenged the use of SCT for treatment in Africa.Stem cell therapy in Africa faces challenges due to human capital flight and barriers to innovation [52].Most countries in the region face a brain drain of skilled professionals, exacerbating healthcare inequities and hindering the establishment of robust cell therapy programs [53].The inability to retain expertise also hinders the development of novel technologies.The innovation chasm between academic research and market-ready products remains a barrier to progress [53,54].Furthermore, financing for research in Africa frequently favours topics that are not as pertinent to the continent, which impedes the development of stem cell therapies [43].The roadblocks to establishing SCT in Africa are diverse and go far beyond the formidable barrier posed by the high cost of treatment.While the expensive costs of licenced gene treatments make universal distribution nearly impossible in low and middle-income countries, additional barriers impede access to modern medical techniques [55].For example, Glybera, being the first gene therapy approved in Europe, cost a startling €1 million and was finally withdrawn due to a lack of coverage in any jurisdiction, owing mostly to its prohibitively high cost [56].Similarly, cancer immunotherapy, typified by the chimeric antigen receptor T cell (CAR-T) product, was initially priced at $475,000, and Zolgensma for spinal muscular atrophy became the most expensive medicine ever marketed, costing $2.125 million [55].Beyond budgetary constraints, LMICs face significant gaps in healthcare infrastructure, such as inadequate neonatal and cancer screening programmes, poor electronic medical record systems, and limited laboratory diagnoses [57].Furthermore, discrepancies in the distribution of standard-of-care treatments, together with common socio-cultural characteristics such as a preference for traditional healing approaches and a lack of medical literacy, limit timely diagnosis and intervention [55,58].
Many countries are without national health insurance programmes, with patients relying on out-of-pocket payments or external funding for their healthcare needs [59].Furthermore, basic care costs for NCDs already burden families' resources, making the prospect of financing gene therapy much more difficult.The lack of affordability causes discrepancies in access, limiting treatment alternatives to the rich [60].While some contend that gene therapy will eventually be more cost-effective than traditional disease management, current estimates indicate otherwise, highlighting the urgent need to investigate cost-cutting strategies.The Global Gene Therapy Initiative has proposed place-of-care bio-manufacturing as a potential option, subject to cooperation from global organisations such as the African Union and the WHO [61].Another challenge is the absence of national guidelines for human gene therapy trials across many African countries.This deficiency poses obstacles to ensuring proper ethical and regulatory processes, particularly in South Africa, where existing regulatory mechanisms are reportedly contradictory and ambiguous [55].Compounding this issue, the involvement of multiple national departments further complicates obtaining necessary ethics and regulatory approvals [62,63].

Potential application of stem cell therapy in Africa Cardiovascular diseases (CVDs)
The potential use of SCT to treat CVDs has been thoroughly reviewed, with emphasis on hPSCs and MSCs [48].Even in phase III trials, there is less evidence to demonstrate the effectiveness of stem cell therapies in increasing newborn size, heart function, or clinical outcomes, despite preclinical and clinical research having largely confirmed the safety of MSCs [31,64].A metaanalysis of 22 trials conducted by Hou et al., (2020), found that bone marrow-derived mononuclear cells significantly increased left ventricular ejection fraction and reduced infarct size in patients with acute myocardial infarction [65].However, no significant cardiac function effects were observed based on myocardial contractility, cardiac remodelling, MRI-derived parameters or clinical outcomes from various stem cell sources [64,65].The unsatisfactory results may be associated with an intensified focus on immune regulation rather than regeneration.To determine the efficacy of these treatments, well-designed phase III studies with rigorous procedures, such as proper cell preparation, patient selection, re-evaluation protocols, and clinical assessments, are required [66].

Gastrointestinal system disorders
Digestive tract diseases account for a considerable proportion of diagnoses in industrialised countries, affecting the lives of roughly one-third of people in the Western world [67].The gastrointestinal system is protected by a single layer of epithelial cells, known for their strong regenerative capacity in response to injury and periodic cell turnover [67,68].These cells are capable of self-renewal and even faster with tissue damage and inflammation due to the presence of stem cells compartmentalised within intestinal crypts [67].Exposure of intestinal stem cells to the gastrointestinal environment can cause direct depletion of the stem cell layer or disturbance of intestinal function, resulting in visible clinical signs [68].Crohn's disease and ulcerative colitis are the two most common inflammatory bowel diseases (IBD) [69].Crohn's disease is characterized by chronic, uncontrollable inflammation of the intestinal mucosa, with symptoms including segmental transmural mucosal inflammation, skip lesions and granulomatosis.Ulcerative colitis, on the other hand, is a chronic inflammatory condition that primarily affects the colon and rectum, with infection starting in the rectum and spreading up to the colon [70].There are two main types of cellular therapy for Crohn's disease: HSC-based therapy and MSC-based therapy [70].Early case studies showed that HSC therapy could lead to long-term remission in some patients, which prompted further investigation.However, a large-scale randomized clinical trial (NCT00297193) conducted by Lindsay et al. (2017)  2011 found no significant differences in clinical outcomes compared to traditional therapy, and concerns about toxicity have been raised [71].Despite the setbacks, systematic reviews and reevaluations of trial outcomes have shown some advantages of HSC therapy over controls in terms of disease activity index improvement [72].HSCs are preferred over MSCs because they produce more consistent results, especially when obtained autologously [73].

Liver disorders
Disruptions in liver homeostasis and function can result in a variety of chronic disorders, including liver failure, cirrhosis, cancer, alcoholic liver disease, nonalcoholic fatty liver disease (NAFLD), and autoimmune liver disease (ALD) [74].While orthotopic liver transplantation remains the only viable treatment for severe liver disorders, the number of acceptable donor organs is extremely restricted.Currently, stem cell therapies for liver illness use HSCs, MSCs, hPSCs, and liver progenitor cells [74,75].Meta-analyses of clinical trials investigating SCT for acute-on-chronic liver failure (ACLF) have revealed short-term clinical advantages, with numerous doses of stem cells often required to extend therapeutic results [74,76].While MSC-based therapy has improved liver functions as measured by the end-stage liver disease score, albumin levels, total bilirubin, and coagulation, there has been no meaningful effect on survival rate or aminotransferase levels [76].However, a randomised controlled trial by Lin et al. (2017) found that hepatic failure from viral hepatitis B treated with allogeneic bone marrow-derived MSCs (BM-MSCs) by peripheral infusion had improved liver function and fewer severe infections and substantially improved the 24-week survival rate in patients with HBV-related ACLF [75][76][77].Liver cirrhosis has been managed with MSCs, and promising clinical outcomes have been reported [77,78].In a clinical trial, patients with chronic hepatitis B and decompensated liver cirrhosis were divided into two groups and given either umbilical cord-derived MSCs or a control treatment [78,79].The MSC group showed a significant reduction in ascites volume and improved liver function, as evidenced by higher serum albumin levels, lower total serum bilirubin levels, and decreased sodium model for end-stage liver disease score [79].Similar results were seen in a phase II trial with bone marrow-derived MSCs among patients with HCV-induced liver cirrhosis [76,78], as well as in three other clinical trials targeting liver cirrhosis caused by hepatitis B and alcoholic cirrhosis [79,80].Recent trials using bone marrow mononuclear cells (BMNCs) in children with liver cirrhosis post-Kasai surgery and in decompensated liver cirrhosis patients demonstrated safety and efficacy in improving liver function [80].However, not all stem cell types or delivery strategies have been effective, as evidenced by a multinational phase 2 experiment in which CD133 + hematopoietic stem cell infusion failed to improve liver abnormalities [81].
Although preclinical studies have shown the efficacy of SCT for improved liver function in NAFLD models, human clinical trials have been limited [82].A recent multicenter clinical trial (UMIN000022601) by Sakai et al. (2021) in Japan treated seven NAFLD patients with freshly extracted autologous adipose-derived stem cells.The data demonstrated elevated serum albumin levels in six individuals and increased prothrombin activity in five patients, with no treatment-related adverse events identified [83].Currently, hematopoietic stem cell transplantation (HSCT) and bone marrow transplantation are the most common stem cell-based therapies that show therapeutic promise in autoimmune liver disease (ALD) clinical trials [57].A study reported that haploidentical HSCTs effectively treated ALD in sickle cell patients, suggesting the potential of this method for dual disease treatment [53].Clinical studies demonstrated that posttransplant immunosuppressive medication led to ALD remission.Primary biliary cholangitis (PBC), a subtype of ALD with progressive loss of bile ducts, has been treated with allogeneic umbilical cord-derived mesenchymal stem cells (UC-MSCs) and UDCA, with promising results [84].In a Chinese trial involving ten PBC patients who had not responded to UDCA for over a year, allogeneic BM-MSCs showed good results with an intravenous infusion [69].

Arthritis and burn treatment
Arthritis refers to a variety of cartilage-related disorders that cause joint discomfort and inflammation.The most common form is osteoarthritis (OA), for which SCT has recently emerged as a potential alternative treatment for osteoarthritis, attracting significant attention in regenerative medicine [85,86].HSCs have effectively reduced bone lesions, promoted bone regeneration, and stimulated rapid vascularization in degenerative cartilage [86].Another study evaluating the efficiency of peripheral blood stem cells in ten OA patients by three intraarticular injections found a significant reduction in the WOMAC index, showing improvement across all criteria [87].To improve the therapeutic potential of HSCT and CD34 + stem cells, they were recommended to be paired with a rehabilitation algorithm across preoperative, hospitalisation, and outpatient periods [87,88].Due to its immunoregulatory and anti-inflammatory qualities, MSC-based therapy for OA is currently gaining traction [88].MSCs have been used as the principal cell source in multiple studies, revealing a favourable safety profile and potential efficacy in pain alleviation, cartilage degradation reduction, and cartilage structure and morphology regeneration in some cases [88,89].However, it is unclear whether bone marrow stem cells, adipose tissue, or the umbilical cord are the best sources of MSCs for OA therapy [89].
A comprehensive evaluation of 61 studies involving over 2390 OA patients found that MSC-based therapy had positive results, albeit with huge evidence and longterm monitoring.Another systematic analysis of 36 clinical trials, including 14 randomised trials, shed light on the potential of autologous MSC-based therapy for OA.Among trials using BM-MSCs, 57% reported significantly superior clinical results than the control group at the 1-year follow-up.Similar results were found for autologous adipose tissue-derived MSCs (AT-MSCs), indicating that clinical outcomes and MRI analysis provide insufficient evidence for MSC therapy's therapeutic potential [88,89].The heterogeneity in outcomes could be attributed to differences in interventions, combination treatments, control treatments, and validated clinical outcome assessments among randomised clinical studies [90].
SCT has effectively treated burns by promoting tissue regeneration and reducing inflammation, promoting angiogenesis, collagen deposition, and cell proliferation, which all help with tissue repair when administered topically or systemically [91].They regulate the immune response by increasing anti-inflammatory substances and inhibiting pro-inflammatory cytokines, which lowers inflammation and stops excessive scarring from forming.This double method of action enhances the results of burn injuries overall, as well as wound healing and tissue regeneration [92].Combining bone marrowderived mesenchymal stem cells (BMSCs) with plateletrich plasma (PRP) has shown significant improvements in burn wound healing in rat models [93].This therapy reduced burn area, faster epithelization, and increased burn contracture rate compared to traditional treatments.It also accelerated wound closure and re-epithelialization by enhancing epidermal cell proliferation and differentiation [93].Angiogenesis, crucial for tissue repair, was promoted through increased expression of vascular endothelial growth factor.The combination therapy also improved scar regulating parameters, decreased oxidative stress, and modulated the inflammatory response [93,94].

Cancer treatment
The use of stem cell therapy in cancer treatment should be carefully discussed and considered by clinicians and researchers to ensure the safety and efficacy of the options.Some stem cell clinics often offer three types of SCTs for cancer treatment: autologous hematopoietic stem cell transplants, stromal vascular fraction, and multipotent stem cells like mesenchymal stem cells.
Allogeneic HSCTs have demonstrated promise in producing donor lymphocytes capable of suppressing and regressing haematological malignancies and some solid tumours, a phenomenon known as the "graft-versustumor regression effect" [95].However, scientific data does not support the safety and efficacy of allogeneic cellbased therapy for treating solid tumours.The Cochrane Library states that marrow transplantation with autologous HSCTs and high-dose chemotherapy does not increase overall survival in women with metastatic breast cancer [96].Additionally, a study of over 41,000 breast cancer patients found no significant difference in survival benefits between those who had HSCTs following highdose chemotherapy and those who received standard treatment [97].
Preclinical studies have highlighted the potential of MSC-based therapy in cancer treatment.MSCs can migrate to injured sites in response to growth factors, cytokines, and chemokines [98].These cells express specific receptors, such as CXCR4 and CCR1-7, which aid in responding to environmental cues.MSCs also have adhesion molecules on their surface, such as CD49d, CD44, CD54, CD102, and CD106, which facilitate attachment, migration, and penetration of blood vessel lumens into injured tissue.Tumors, like injured tissues, generate chemoattractants that induce MSC migration via the CXCL12/CXCR4 axis [99].Once MSCs migrate to malignant tissue, they can interact with cancer cells, demonstrating both protumor and antitumor effects, which are crucial considerations in MSC-based therapy.MSCs are known for their regenerative abilities, which promote tissue repair and recovery.They also have unique abilities that contribute to their protumor behavior.Studies have shown that breast cancer cells increase MSC production of chemokine (C-C motif ) ligand 5 (CCL-5), which regulates tumour invasion [100].MSCs also release growth factors such as VEGF, basic FGF, HGF, and PDGF, which can suppress cancer cell death.Despite their role in protumor activities, MSCs have significant tumor-suppressive properties that have been used in cancer treatment [99].They can block the Wnt and AKT signalling pathways, decrease angiogenesis, increase inflammatory cell infiltration, and trigger tumor cell cycle arrest and apoptosis.However, the specific roles of MSCs in both protumor and anticancer actions remain debatable in the stem cell field [26,101].
Numerous clinical trials have been profiled on Clini-calTrials.gov to examine the potential of mesenchymal stem cells (MSCs) as a cancer treatment.These trials, mostly phase 1 and 2 studies, aim to evaluate the safety and efficacy of MSC-based therapy [102].Some researchers have investigated combining MSC-based therapy with an oncolytic viral approach, which involves using viruses that selectively infect and kill cancer cells while leaving healthy cells unharmed [103].For example, a study by Rincón et al. (2017) utilised bone marrow-derived MSCs infected with the oncolytic adenovirus ICOVIR5 to treat metastatic and resistant solid tumours in both pediatric and adult patients.The study demonstrated the treatment's safety and provided preliminary evidence of its therapeutic potential [104].Another study published in 2019 showed that adipose-derived MSCs injected with the vaccinia virus could eradicate resistant tumor cells by enhancing virus amplification and sensitising tumour cells to virus infection [105].

Diabetes
Since the pancreas has limited regenerative capacity for its islets, alternative cell sources are being explored in cases of failure.PSCs are highly regarded for their potential in beta cell replacement therapies.Several clinical trials are underway to replace beta cells using ESCs [106].These trials involve implanting insulin-producing beta cells within an encapsulating device beneath the skin to protect them from autoimmune attacks in type 1 diabetes patients [107].One example of such a trial is the phase I/ II trial launched by ViaCyteTM in partnership with Harvard University in 2014, which involves 40 patients and uses two subcutaneous capsules containing insulin-producing beta cells generated from ESCs.Preclinical studies have shown successful blood sugar correction and viable, intact insulin-producing cells after 174 days [108].
Treating diabetic foot ulcers (DFUs) in Africa using SCT is a multifaceted process influenced by preclinical and clinical studies.BM-MSCs are typically preferred in clinical settings, with autologous cells being the preferred choice [96].However, the choice of stem cell type remains controversial, with bone marrow and peripheral blood-derived MSCs also being used frequently [109].Adipose-derived stem cells (ADSCs) are preferred due to their simpler isolation methods and promising outcomes.However, challenges such as metabolic changes and advanced age in DFU patients necessitate alternative approaches like allogeneic therapy [109].Both local and systemic delivery routes have shown efficacy, with local injections being the most common method.Bioengineered products like Graftjacket and Epifix offer promising avenues for stem cell therapy delivery.Further research is needed to optimize the use of stem cell therapy for DFU treatment in Africa.

Neurological disorders
SCT holds significant promise in the realm of neurological disorders, particularly in conditions like Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), glioblastoma multiforme (GBM), and ischemic stroke (IS).

Alzheimer's disease (AD)
MSCs can repair injured neurons, lessen cell death, and remove harmful aggregates linked to the pathophysiology of AD [44].Research has demonstrated that in animal models of AD, MSC transplantation can lower Tau phosphorylation, enhance cognitive performance, and lessen inflammation.Additionally, increased neurogenesis following MSC transplantation has been linked to the amelioration of AD-like diseases.Furthermore, using MSC-derived exosomes loaded with miRNAslike miR-29a and miR-21-has demonstrated encouraging outcomes in lowering Aβ levels and delaying the decline of cognitive function in AD models.The clinical trial (NCT05233774) has also shown enhanced cognition scores and increased hippocampus volume, indicating the safety and possible effectiveness of MSC transplantation in AD patients [110].

Parkinson's disease (PD)
MSCs have been reported to treat motor and non-motor symptoms in Parkinson's disease.Through trophic activities fueled by cytokines, neuroprotective factors, and differentiation into unique cell types that aid in cell replenishment, MSC transplantation alters disease symptoms and development.Numerous MSC transplantation strategies, including autologous and allogeneic methods, as well as the application of the MSC secretome, have been investigated in studies [111].To alter the course of the disease and manage its symptoms, clinical trials assessing the safety and effectiveness of MSC-based therapy in PD patients are now being conducted [112].

Multiple sclerosis (MS)
MSCs and their exosomes have emerged as prospective treatment alternatives for MS given their capacity to lessen neuroinflammation, enhance remyelination, and ameliorate motor function deficiencies.Exosomes produced from MSCs have been demonstrated in studies to reduce proinflammatory responses and lessen demyelination in MS models.Clinical studies with the identifier NCT02166021 have looked into the effectiveness and safety of MSC transplantation in MS patients [113,114].According to this experiment, MSCs seem to be a promising therapy option for multiple sclerosis, with intrathecal application being the most effective mode of administration.Some studies have also shown improvements in neurological function and a decrease in disease activity [115].

Glioblastoma Multiforme (GBM)
GBM's aggressiveness and intricate tumor microenvironment provide special challenges.Studies have investigated the administration of anti-cancer medicines, including microRNAs and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), via MSCs, although care is advised due to their possible role in tumor progression.With an emphasis on tactics such as oncolytic virus-loaded MSCs and suicide gene-expressing MSCs, clinical trials (NCT03896568 and NCT04657315) are being conducted to assess the safety and effectiveness of MSC-based therapy in GBM patients [113,116].

Ischemic stroke (IS)
MSC transplantation has demonstrated potential for improving vascularization and neurogenesis, decreasing infarct volume, and accelerating neurological recovery in IS [116].Research has looked into several delivery methods and cell sources, such as MSCs produced from bone marrow and umbilical cord, as well as the use of exosomes derived from MSCs that are loaded with neuroprotective microRNAs.Clinical investigations such as NCT01716481, NCT01461720, NCT04280003, NCT00875654, and NCT04280003 have all indicated improvements in motor function and biomarkers linked to neurogenesis and neuroplasticity, as well as the safety of MSC transplantation in IS patients [113].

Recommendations
To enhance SCT in Africa, it is critical to build a strong regulatory framework that meets international standards.This framework should establish clear criteria for the derivation, processing, and clinical application of stem cells, as well as protect patients from fraudulent practices.Furthermore, there is an increasing need to engage in capacity building by offering financial incentives to dissuade qualified workers from migrating and boosting stem cell education to cultivate and keep talent in African countries.Efforts should be made to guarantee that SCT is affordable to the general population.This can be accomplished by providing government subsidies for medical insurance and advocating for the inclusion of SCT in various medical insurance policies.Addressing religious resistance is also critical; educational activities aimed at religious communities can debunk myths and promote informed decision-making regarding support for stem cell research.Extensive public education campaigns are required to improve knowledge of stem cells, their potential advantages, and their role in disease treatment, such as HIV/AIDS.These efforts should try to dispel myths, provide factual information, and demonstrate the practical benefits of SCT using examples and testimonies.Finally, showing the safety and efficacy of SCTs using empirical evidence might help ease scepticism and anxieties, eventually leading to greater acceptance of stem cells.

Conclusion
In conclusion, SCT appears to be a promising path for improving health outcomes among Africans suffering from neurodegenerative illnesses and most non-communicable diseases.Despite significant progress made in animal studies and clinical trials, further refining is required to maximise cell therapy's efficacy in the human body.Nonetheless, scientists' major advances encourage confidence in SCT's ability to tackle neurodegenerative disorders effectively.Continued devotion and innovation in this discipline present promising opportunities for improving many people's lives impacted by these disorders.Furthermore, SCT is moving from a theoretical possibility to a physical reality, thanks to a decade of intense study.Despite ongoing hurdles, the discipline has made significant progress, with successful clinical studies for diseases such as neurodegenerative disorders and macular degeneration.Notably, iPSCs are revolutionising research by providing personalised treatment choices based on patients' cells.Furthermore, the clinical use of MSCs to regenerate dental and periodontal tissues demonstrates the near-term viability of SCTs.Despite formidable challenges, rapid advancements in stem cell research pave the way for the widespread adoption of cellular therapeutics.Globally, concerted efforts are underway to establish regulatory guidelines and standards to ensure patient safety.The emergence of SCTs is poised to profoundly impact human health, offering new avenues for treating a myriad of debilitating conditions.

NCT NUMBERS References Study Title Study Status Brief Summary Interventions Sponsor Study Type Arthritis and Musculoskeletal system studies/interventions
fistulas in patients with Crohn's disease.The objective is to get a homogeneous implementation in all hospitals in Spain that have been baked to use this biological therapy.

Table 1
List of completed clinical trials on the use of Stem Cell Therapy in non-communicable diseases [49]nced in other African countries, such as Tunisia, Egypt, Morocco, Algeria, and Libya[49].

Table 2
List of active clinical trials on the use of stem cell therapy in non-communicable diseases